Phase 2
Completed N=240
Study of the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Fosaprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV) in Children (MK-0517-029)
Source: ClinicalTrials.gov NCT01697579 ↗Enrolled (actual)
240
Serious AEs
37.0%
Results posted
Nov 2017
Primary outcomePrimary: Maximum Concentration (Cmax) of Aprepitant in Participants 0 to <2 Years of Age — 3550 ng/mL
Summary
The purpose of this study was to determine the appropriate dosing regimen of fosaprepitant, when administered with ondansetron (with or without dexamethasone), for the prevention of CINV in children from birth to <17 years of age. Fosaprepitant is a prodrug to aprepitant. All participants who completed the randomized Cycle 1 could elect to receive open-label fosaprepitant during optional Cycles 2-6.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Concentration (Cmax) of Aprepitant in Participants 0 to <2 Years of Age |
3550 | — |
| PRIMARY Time to Maximum Concentration (Tmax) of Aprepitant in Participants 0 to <2 Years of Age |
2.01 | — |
| PRIMARY Area Under the Concentration-time Curve of Aprepitant From Time 0 to Infinity (AUC 0-∞) in Participants 0 to <2 Years of Age |
37200 | — |
| PRIMARY Area Under the Concentration-time Curve of Aprepitant From Time 0 to 24 Hours (AUC 0-24hr) in Participants 0 to <2 Years of Age |
36800 | — |
| PRIMARY Apparent Terminal Half-life (t1/2) of Aprepitant in Participants 0 to <2 Years of Age |
7.94 | — |
| PRIMARY Concentration of Aprepitant After 24 Hours (C24hr) in Participants 0 to <2 Years of Age |
691 | — |
| PRIMARY Concentration of Aprepitant After 48 Hours (C48hr) in Participants 0 to <2 Years of Age |
352 | — |
| PRIMARY Apparent Total Body Clearance (CL/F) of Aprepitant in Participants 0 to <2 Years of Age |
24.2 | — |
| PRIMARY Cmax of Aprepitant in Participants 2 to <6 Years of Age |
4270; 2320; 2030; 323 | — |
| PRIMARY Tmax of Aprepitant in Participants 2 to <6 Years of Age |
1.90; 2.29; 1.36; 1.34 | — |
| PRIMARY AUC 0-∞ of Aprepitant in Participants 2 to <6 Years of Age |
46400; 15300; 16000; 2070 | — |
| PRIMARY AUC 0-24hr of Aprepitant in Participants 2 to <6 Years of Age |
45000; 21800; 19700; 1840 | — |
| PRIMARY t1/2 of Aprepitant in Participants 2 to <6 Years of Age |
9.27; 6.55; 7.27; 6.18 | — |
| PRIMARY C24hr of Aprepitant in Participants 2 to <6 Years of Age |
1060; 278; 332; 9.23 | — |
| PRIMARY C48hr of Aprepitant in Participants 2 to <6 Years of Age |
232 | — |
| PRIMARY CL/F of Aprepitant in Participants 2 to <6 Years of Age |
31.8; 66.2; 29.6; 48.5 | — |
| PRIMARY Cmax of Aprepitant in Participants 6 to <12 Years of Age |
4400; 3550; 1360; 507 | — |
| PRIMARY Tmax of Aprepitant in Participants 6 to <12 Years of Age |
2.92; 1.99; 2.14; 1.68 | — |
| PRIMARY AUC 0-∞ of Aprepitant in Participants 6 to <12 Years of Age |
55300; 34300; 10700; 2860 | — |
| PRIMARY AUC 0-24hr of Aprepitant in Participants 6 to <12 Years of Age |
47400; 29200; 12000; 4260 | — |
| PRIMARY t1/2 of Aprepitant in Participants 6 to <12 Years of Age |
9.77; 7.69; 8.23; 6.58 | — |
| PRIMARY C24hr of Aprepitant in Participants 6 to <12 Years of Age |
1210; 589; 219; 70.4 | — |
| PRIMARY C48hr of Aprepitant in Participants 6 to <12 Years of Age |
164 | — |
| PRIMARY CL/F of Aprepitant in Participants 6 to <12 Years of Age |
42.1; 69.2; 78.8; 89.6 | — |
| PRIMARY Cmax of Aprepitant in Participants 12 to 17 Years of Age |
3500; 1180; 582 | — |
| PRIMARY Tmax of Aprepitant in Participants 12 to 17 Years of Age |
0.546; 0.722; 0.736 | — |
| PRIMARY AUC 0-∞ of Aprepitant in Participants 12 to 17 Years of Age |
33800; 12300; 3500 | — |
| PRIMARY AUC 0-24hr of Aprepitant in Participants 12 to 17 Years of Age |
30400; 9700; 4820 | — |
| PRIMARY t1/2 of Aprepitant in Participants 12 to 17 Years of Age Hours |
10.5; 7.92; 8.27 | — |
| PRIMARY C24hr of Aprepitant in Participants 12 to 17 Years of Age |
735; 142; 101 | — |
| PRIMARY C48hr of Aprepitant in Participants 12 to 17 Years of Age |
— | — |
| PRIMARY CL/F of Aprepitant in Participants 12 to 17 Years of Age |
76.2; 91.7; 105 | — |
| PRIMARY Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycle 1 |
87.8; 83.3; 90.7; 80.0; 77.1 | — |
| PRIMARY Percentage of Participants Who Experienced at Least One Adverse Event (AE) in Cycles 2-6 |
93.6; 75.5 | — |
Eligibility Criteria
Inclusion Criteria
- Is 0 months (at least 37 weeks gestation) to <18 years of age
- Scheduled to receive chemotherapeutic agent(s) associated with moderate, high, or very high risk of emetogenicity for no more than 5 consecutive days for a documented malignancy, or a chemotherapy regimen not previously tolerated due to vomiting
- Expected to receive ondansetron as part of antiemetic regimen (Cycle 1); Expected to receive a 5-HT3 antagonist as part of antiemetic regimen (Cycles 2-6)
- If female and has begun menstruating, must have a negative pregnancy test prior to study participation and agree to remain abstinent or use a barrier form of contraception
- Predicted life expectancy of ≥3 months
- Pre-existing functioning central venous catheter
- Weight ≥3rd percentile for age and gender (and ≥3.0 kg)
Exclusion Criteria
- Vomited in the 24 hours prior study drug administration (Cycle 1)
- Current user of any illicit drugs (including marijuana) or current evidence of alcohol abuse
- Scheduled to receive stem cell rescue therapy in conjunction with study related course(s) of emetogenic chemotherapy
- Received or will receive radiation therapy to the abdomen or pelvis in the week prior to study drug administration and/or during the course of the study
- Pregnant or breast feeding
- Allergic to fosaprepitant, aprepitant, ondansetron, or any other 5-HT3 antagonist
- Has a symptomatic central nervous system (CNS) tumor causing nausea and/or vomiting
- Has an active infection, congestive heart failure, slow heart rate, or other uncontrolled disease other than cancer
- Mentally incapacitated or has a significant emotional or psychiatric disorder
- Known history of QT prolongation or is taking any medication known to lead to QT prolongation
- Taking other excluded medications
- Participated in any previous study of aprepitant or fosaprepitant, or taken an investigational drug within 4 weeks prior to study participation
Data sourced from ClinicalTrials.gov (NCT01697579). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.